Crystal Structure of Tryptophan Lyase (NosL): Evidence for Radical Formation at the Amino Group of Tryptophan1. Issue 44 (5th September 2014)

• Record Type: Journal Article
• Authors: Nicolet, Yvain; Zeppieri, Laura; Amara, Patricia; Fontecilla‐Camps, Juan C.
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 44(2014)
• Page Start: 11840
• Page End: 11844
• Publication Date: 2014-09-05
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201407320
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Streptomyces actuosus tryptophan lyase (NosL) is a radical SAM enzyme which catalyzes the synthesis of 3‐methyl‐2‐indolic acid, a precursor in the synthesis of the promising antibiotic nosiheptide. The reaction involves cleavage of the tryptophan CαCβ bond and recombination of the amino‐acid‐derived ‐COOH fragment at the indole ring. Reported herein is the 1.8 Å resolution crystal structure of NosL complexed with its substrate. Unexpectedly, only one of the tryptophan amino hydrogen atoms is optimally placed for H abstraction by the SAM‐derived 5′‐deoxyadenosyl radical. This orientation, in turn, rules out the previously proposed delocalized indole radical as the species which undergoes CαCβ bond cleavage. Instead, stereochemical considerations indicate that the reactive intermediate is a ^.NH tryptophanyl radical. A structure‐based amino acid sequence comparison of NosL with the tyrosine lyases ThiH and HydG strongly suggests that an equivalent ^.NH radical operates in the latter enzymes.</p> </abstract>